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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis
New England Journal of Medicine, Volume 370, No. 26, Year 2014
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Description
BACKGROUND: Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome-related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered. METHODS: We assessed survival at 26 weeks among 177 human immunodeficiency virus-infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole. RESULTS: The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P = 0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P = 0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P = 0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P = 0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups. CONCLUSIONS: Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. Copyright © 2014 Massachusetts Medical Society.
Authors & Co-Authors
Boulware, David R.
United States, Minneapolis
University of Minnesota Twin Cities
Meya, David B.
United States, Minneapolis
University of Minnesota Twin Cities
Uganda, Kampala
Makerere University
Muzoora, Conrad K.
Uganda, Mbarara
Mbarara University of Science and Technology
Rolfes, Melissa A.R.
United States, Minneapolis
University of Minnesota Twin Cities
Hullsiek, Katherine Huppler
United States, Minneapolis
University of Minnesota Twin Cities
Musubire, Abdu Kisekka
Uganda, Kampala
Makerere University
Taseera, Kabanda
Uganda, Mbarara
Mbarara University of Science and Technology
Nabeta, Henry W.
Uganda, Kampala
Makerere University
Schutz, Charlotte
South Africa, Cape Town
University of Cape Town
Williams, Darlisha A.
United States, Minneapolis
University of Minnesota Twin Cities
Uganda, Kampala
Makerere University
Rajasingham, Radha
United States, Minneapolis
University of Minnesota Twin Cities
Uganda, Kampala
Makerere University
Rhein, Joshua R.
United States, Minneapolis
University of Minnesota Twin Cities
Uganda, Kampala
Makerere University
Thienemann, Friedrich
South Africa, Cape Town
University of Cape Town
Lo, Melanie W.
United States, Minneapolis
University of Minnesota Twin Cities
Uganda, Kampala
Makerere University
Nielsen, Kirsten N.
United States, Minneapolis
University of Minnesota Twin Cities
Bergemann, Tracy L.
United States, Minneapolis
University of Minnesota Twin Cities
Kambugu, Andrew Ddungu
Uganda, Kampala
Makerere University
Manabe, Yukari C.
Uganda, Kampala
Makerere University
United States, Baltimore
Johns Hopkins School of Medicine
Janoff, Edward N.J.
United States, Aurora
University of Colorado Anschutz Medical Campus
United States
Va Medical Center
Bohjanen, Paul R.
United States, Minneapolis
University of Minnesota Twin Cities
Meintjes, Graeme Ayton
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
Statistics
Citations: 389
Authors: 21
Affiliations: 8
Identifiers
Doi:
10.1056/NEJMoa1312884
ISSN:
00284793
e-ISSN:
15334406
Research Areas
Environmental
Study Design
Randomised Control Trial
Cohort Study
Study Locations
South Africa
Uganda